DE3326180A1 - 1-PHENOXY- (PHENYLTHIO) -4-ARYLALKINYLOXY-BENZOL DERIVATIVES AND THEIR USE - Google Patents

Description

PATENT LAWYERS

dr. V. SCHMIED-KOWARZIK · dr. P. WEINHOLD · dr. P. BARZ · Munich;. G. DANNENBERG · dr. D. GUDEL- dipl.-inc. S. SCHUBERT · Frankfurt

APPROVED REPRESENTATIVES AT THE EUROPEAN PATENT OFFICE

SIECFRIEDSTRASSE β aOOO MÖNCHEN * O

PHONE! (069) 335024 + 335025 TELEGRAMS: WIRPATENTS TELEX! 5215679

SK / SK; Case F.3117

Montedison S.p.A. 31, Foro Buonaparte Milan / Italy

1-phenoxy- (phenylthio) -4-arylalkinyloxy-benzene derivatives and their uses.

_ 2T _

The present invention relates to l-phenoxy- (phenylthio) -4-aryl-alkinyloxy-benzene derivatives, those an insect juvenile hormone activity and an acaricidal activity own.

The present invention further relates to the use thereof for controlling acarid and insect infestations as well as the production of these connections.

"Compounds with juvenile hormone activity" or "juvenile hormones" for short refer in the present invention to those compounds which - although they are not natural juvenile hormones of insects - nevertheless have similar properties thereof. When these compounds come into contact with Juvenilformen insects, _w ith eg larvae Neanide or even embryo in the egg, they can insect development, depending on the time and the dose administered beeinflusseiji, and, depending on the type, they cause also the death of the individual insect or severe deformities that lead to death or to individuals who can no longer reproduce.

Even when used against adult forms, these compounds can prove to be active, causing insect reproduction To prevent inhibition of oviposition or hatching. The use of compounds with juvenile hormone activity offers significant environmental benefits compared to common insecticides; in fact they are juvenile hormones highly selective, which is why they do not damage any useful species and, in particular, are not very toxic to warm-blooded animals and fish are.

Various compounds having juvenile hormone activity are known such as those disclosed in U.S. Patents 4,061,683, 4,141,921 and U.S. Pat 4,153,731, in GB-PS 2,023,591 and US-PS 4,126,623.

New compounds have now been found which are the object of the present invention and have the general formula to have:

0-C-CSC-.R

in which

R = a 2-furyl, 2-thienyl, pyridyl or phenyl radical, where the pyridyl or phenyl radical is optionally replaced by one or more groups selected from C 1-6 alkyl, C ₅ haloalkyl with 1 to 3 halogen atoms, C " _ ₅ alkenyl, C _3-5 haloalkenyl having 1 to 3 halogen atoms, C ~ _, - alkynyl, C, - alkoxy, ^C l-5 ^Ha l ° 9 ^ena l ^ ^ox y Rait 1 to 3 halogen atoms, C, ₅ Alkylthio, alkoxycarbonyl with 1 to 5 carbon atoms in the alkoxy part, alkylcarbonyl with 1 to 5 carbon atoms in the alkyl part, nitro, cyano and halogen, can be substituted,

X = an oxygen atom or a divalent sulfur atom;

1 2
R and R = which are the same or different from one another, are a hydrogen atom or a methyl or ethyl group.

The compounds of the formula I have juvenile hormone activity and are suitable for use in insect control. The compounds of formula I are prepared by two alternative methods can be produced, which comprise reactions known per se in organic chemistry.

The choice between the two methods depends essentially ₃₀ of the particular compound to be prepared from, as a function of the reactivity of the corresponding intermediate products in the individual reactions of the procedure.

Procedure 1

i-a)

ο.

(H)

0 M.

- C = CH

(III)

RIC - C Ξ CH ι *

(IV)

1-b) (IV) + Y-R

Procedure 2

2-a) ZC-C = CH 20 R ²

(III)

- R -> Z -

(V)

C - C = C -R A *

(VI)

2 B)

(VI)

(I)

(H)

1 2 In the above reactions, R, R, R and X have the for formula

I specified meaning; M ⁺ stands for the cation of an alkali metal (sodium or potassium), Z stands for a chlorine or bromine atom or a tosyl group (p-toluenesulphonate), and X is a bromine or iodine atom.

The compound (II) is the alkali salt of 4-phenoxyphenol or 4-phenylthiophenol, which is usually found in the reaction medium the corresponding phenol and an alkaline base (sodium or potassium hydroxide, potassium carbonate, etc.).

The alkynes of the formula (III) are compounds known as halides (Z = Cl, Br) or alcohols (Z = OH), the corresponding tosylate (Z = tosyl) from the latter easily can be prepared by reaction with tosyl chloride.

The compound of formula (V) (Y - R) is an aromatic halogen compound; if Y = Br it is e.g. 2-bromofuran, 2-bromothiophene, Bromopyridine or bromobenzene, where the last two compounds are optionally given for formula (I) Way can be substituted.

The reactions 1-a and 2-b take place by in a geeig Neten polar solvent produces the alkali salt (II) (from the corresponding phenol and an alkaline base) and the alkyne (III) or (IV) per se or dissolved in a suitable solvent is added to the salt solution or suspension.

Reactions 1-b and. 2-a take place in the presence of a Nickel or palladium complex as a catalyst according to the method described in L. Cassar, J. Organometallic Chem. ^ _3, 253 (1975) or by

described K.Sonogashira et al, Tetr.Lett. 5_0, 4467 (1975) / method.

In particular, reaction 2-a takes place appropriately when the alkyne of the formula (III) has a functional alcohol group (Z = OH) which can be easily converted into the corresponding {halide or tosylate after the reaction.

Some of the compounds of formula (IV) and in particular the l-phenoxy-4-propargyloxybenzene and l-phenoxy-4- (butin-3-yloxy) benzene have been described as juvenile hormones in US Pat. No. 4,141,921. Their juvenile hormone activity is however significantly lower than that of the compounds of formula (I).

As stated above, the compounds of the formula (I) have juvenile hormone activity. This activity shows itself in very low doses, against both larvae and insect eggs.

- JS -

The insects against which the compounds of formula (I) have been found to be effective include the important species from Coleoptera, Lepidoptera, Diptera, Hymenoptera, Hemiptera 5 Orthoptera and Siphonaptera.

An interesting collateral activity is the acaricidal acti vity against acarid eggs, this property in compounds with juvenile hormone activity right. unusual is 10

Furthermore, the compounds of the formula (I) are not very toxic to warm-blooded animals and fish.

Due to their high activity, even in very low doses,

'' 15 due to their activity spectrum and their low toxicity

The compounds of the formula (I) are particularly suitable for use in combating insect infestation in agriculture as well as in general. For practical purposes they are insecticidal per se or, preferably, as suitable Composition used. In addition to one or more compounds of the formula, these compositions contain (I) as an active ingredient, a solid or liquid inert carrier and optionally other additives that are customary ι be used in such formulations, such as surface-active agents, wetting agents, antioxidants, suspending agents, means promoting liability, etc.

j The compounds of the formula (I) can also be used to

j tongues are made in the form of feed baits, which are suitable for controlling certain types of insects which are harmful both in agriculture and in general. In general the baits consist of a solid or liquid food substance that is attractive to the insect, on or in which the compound of formula (I) is given. The bait continued to come in the usual way, corresponding to the particular purpose Supplements included.

Optionally one can use the insecticidal compositions also add other compatible active substances which, depending on the intended purpose, can be derived from common insects ticides, acaricides ^ fungicides, etc.

In accordance with standard formulation practice, the insecticidal compositions can in the form of emulsifiable concentrates, liquid concentrates, dispersions, pastes, powders, granulates, wettable ones Powder, etc.

The amount of the compound of formula (I) to be used depends on j on various factors such as the relative potency of the particular compound of formula (I) chosen, the the insect species to be controlled, the type and extent of the infestation, the infested location (in the household or in an inhabited area, Stables, crops, pastures, watercourses, feed, other places used by humans or i Animals are frequented, the animals themselves, etc.), and climatic and environmental conditions. In general, amounts of product will suffice from 1 to 1000 g / ha for use in agriculture, in the household or in an inhabited environment. For others Purposes, the amount of compound is calculated taking into account the above factors.

The following examples illustrate the present Invention.

Example 1_

Preparation of 1-phenoxy-4 -, ^ 2- (2-pyriäyl) -prop-2-ynyloxy-7-benzene; Compound No. 1 of the formula:

r3j ° Xol

\ / v ^ - "^ · 0 - CH ₂ - C = C

Procedure a

Into a 100 ml flask equipped with a stirrer, thermometer and reflux condenser and kept in a nitrogen atmosphere were introduced: 20 ml dimethylformamide, 1.1 g (5 χ ΙΟ ""'j mol) l-phenoxy-4-propargyloxy-benzene ( prepared according to US Pat. No. 4,141,921), 0.81 g (5 10 ^-3 mol) 2-broir.pyridine, 0.25 σ |

Palladium-bis-triphenylphosphine dichloride ^ d / PiC ^ -H, -) J ~ χ Cl

0.24 g (6 10 mol) of ground NaOH and 0.15 g of copper-I-iodide / CuJ7. ^{The reaction mixture was heated to 100 °} C. for 4 h with stirring in a nitrogen atmosphere. After cooling, the mixture was poured into water and extracted with ethyl ether. The ethereal extracts were collected and washed neutral with water; then they were dried over anhydrous sodium sulfate. Subsequently, the solvent] was removed by evaporation under reduced pressure, and the ₁₀ residue was purified by chromatography on a silica gel column (eluent 7: 3 hexane: ethyl ether) gereinigt.So was obtained 0.9 g of the desired product as a crystalline solid; M.p. 74 ° C.
Procedure b

₁₅ Into a 250 ml flask equipped with a stirrer, thermometer and reflux condenser and kept in a nitrogen atmosphere were introduced: 80 ml of triethylamine, 6.16 g (27.5 × 10 mol) of 1-phenoxy-4-propargyloxybenzene, 4.35 g (27.5 χ 10 mol) of 2-bromopyridine, 140 mg of palladium-bis-triphenylphosphine dichloride and 80 mg of copper-I-iodide. The reaction mixture was refluxed for 4 hours. After cooling, 100 ml of ethyl ether were added and the solid trimethylammonium bromide obtained was filtered off. The solvents were eliminated under reduced pressure and the residue by chromatography on a

₂ 5 alumina column (eluent 7: 3 hexane: ethyl ether) cleaned. 4.7 g of the desired product were obtained in this way;

M.p. 74 ° C.
1
H - NMR (CDCl ₃ , TMS)

cT (ppm): 4.87 (s, 2H), 6.77-7.82 (m, 12H), 8.40-8.62 (m, IH) ₃₀ (s = singlet, m = multiplet or not -separated complex signal).

Example 2

Preparation of l-phenoxy-4- / 3- (4-methoxyphenyl) prop-2-ynyloxy / benzene; Compound No. 2 of the formula

-A-

The preparation took place as in Example 1, method a, starting from 1-phenoxy-4-propargyloxybenzene and 4-bromanisole. Compound No. 2 was a white solid: ¹ H-NMR (CDCl -., TMS)

: 3.75 (s, 3H), 4.85 (s _f 2H), 6.70-7.45 (m, 13H).

Example 3

Preparation of l-phenoxy-4- / 3- (4-methylphenyl) prop-2-ynyloxyy'-benzene; Compound No. 3 of the formula r- ^ V

foj

- CH ₂ - CSC - ^ O) ^CH 3 ⁽³⁾

The preparation was carried out as in Example 1, method a, starting from 1-phenoxy-4-propargyloxybenzene and 4-bromotoluene. Compound No. 3 was a white solid; ¹ H-NMR (CDCl ₃ , TMS)

: 2.30 (s, 3H), 4.80 (s, 2H), 6.78-7.42 (m, 13H).

Example 4_

Preparation of l-phenoxy-4- / 3- (4-nitrophenyl) prop-2-ynyl-20oxy / benzene; Compound No. 4 of the formula

The preparation was carried out as in Example 1, method b, starting from 1-phenoxy-4-propargyloxybenzene and 4-nitrobromobenzene. Compound No. 4 was a crystalline solid; Mp 125 ° C.
Example 5_

Preparation of l-phenoxy-4- (3-phenyl-prop-2-ynyloxy) -benzene; Compound No. 5 of the formula

The preparation was carried out as in Example 1, method b, starting from l-phenoxy-4-propargyloxybenzene and iodobenzene. Compound No. 5 was a liquid at room temperature; ¹ H-NMR (CDCl ₃₁ TMS)
/ (ppm): 4.85 Cs, 2H), 6.80-7.75 (m, 14H).

"4L · '

example

The compounds listed in Table 1 were prepared according to the method described in Example 1: Table 1

Compounds of formula (I):

Connection ¹⁵ No. (2)

1 2 3 4 5 6

I 2-i> yridyl

4-CH ₃ OC ₆ H ₄ 4-CH ₃ -C ₆ H ₄

2-thienyl

4-ClLCO-CH ₄ 3 ο

C - C = C - R

H H H H H H H

H
H
H
H
H
H
H

0 0 0 0 0 0 0

(3)

F.

CC)

74

Solid

125

oil

52-3

: R
1 ** '15 ' R ² 3326180 X
I. F.
( ⁰ C) 51-3 Connection
₅ no .; (2) t
4-CN-C ₆ H ₄ R ¹ II \ \
0 105-7
1 48-5Ο 8th j 4-CF-CH
3 6 4 H H 0 73-4 76-7 9 , 4-Cl-C, H.
! 6 4 H ; H ί
0 30-1 oil io 10 j 2-pyridyl H H O oil
- Il 11th ■ 4-CH ₃ OC ₆ II ₄ ^CII 3 H 0: ■ 0; " 12th j4-Br-C ₆ H ₄ ^CH 3 H 0 ■ 90-1
ι 13th
15th ι 4-P yridy I. H H ο: oil 14th ¹ 2 63
2 ~ 6 3 H H
H
H 1
0 j 83-4
i
0! oil
\
0: " 15th
16
20th
17th 2- (COOCH) -C, H
3 64 H
H
^CH 3 H 0! »
I. 18th C, H.
6 5 H H s ■ 75 19th C.II
6 5
2-pyridyl H H
H s ^! 01
S ^: " ²⁵ 20
21 2-pyridyl ^C11 3
H H S ■ " 22nd ⁴ - ^F - ^C 6 ^H 4 ^CH 3 H 0 55-6 30 23 2-CH ₀ -C, II
364 H H 0 24 2-CH ₃ OC ₀ H ₄ H H O 25th 4-CH ₃ OC ₆ H ₄ ^CEI 3 H S. 35 ²⁶ 4-CH ₃ OC ₆ H ₄ H H S. 27 2-pyridyl ^C1I 3 ^C1I 3 0 28 4-CH ₃ OC ₆ H ₄ ^CH 3 ^CH 3 29 ^CH 3 I.

Connection R. No.; (2) 5 30th ' 2-CH ₀ OC, H.
3 04 31 ! 3-CH -CH.
3 64 32 5-C3-2-eyridyl 10 33 , 5-Cl-2-pyridyl 34 '5-Cl-2-pyridyl 35 4-CH OC H.
3 64 15th 36 2-pyridyl 37 5-CH -2-pyridyl 38 4-CH -2-pyridyl 20th 39 6-CH -2-pyridyl

^CH 3 H

^CH 3

^CH 3 H

^CH 3

^CH 3

H
H

R "

CH,
H

^CH 3
H

^CH 3

^CH 3
H

O O O O O S S O O O

(3)

F. ( ⁰ C)

oil

71-3

oil

Il

82-4 60-1

oil

(1) the spectroscopic H-NMR data of all compounds ent

languages of the adopted structure

(2) Compounds 1 to 5 are described in Examples 1 to 5

(3) the melting points were not corrected: the compounds designated as oils are thick oils at room temperature, which in most cases solidify when they are cooled ^{to around -10 to 0 ° C.}

Example 7_

Determination of the biological activity of the compounds of

Table 1 of Example 6.

Determination of juvenile hormone activity

1) Spodoptera littoralis (Lipidoptera) larvae 350 to 36 h old 6th instar larvae were treated by one topically through microsyringe 2 μΐ of an acetone solution of the product applied to the first two jurosternites.

As a control, another group of larvae of the same age was treated under the same conditions, but only with acetone.

The insects were kept in the presence of artificial food and sawdust at 25 + 1 ⁰ C and 65 + 5% relative humidity so that the larvae became chrysalids. Hormone activity is expressed as the percentage of abnormal live and dead insects (larvae, chrysalids and adults) corrected for the control according to Abbott; it was determined when the insects not treated with the product had completely stopped escaping from the cocoon (control) (about 20 days after the treatment). Compounds # 1, 2 and 3 showed complete activity (100%) at doses of 200 / insect.
2 | _Aedes_aegYpti_ | Diptera2_Larven
3 ml of an acetone solution of the product and then 25 larvae of the 3rd and 4th instar were introduced into pots each containing 297 ml of spring water, after which the pots were sealed with gauze. The control was carried out in the same way by introducing larvae into pots containing 300 ml of spring water. The samples were kept at 27 ° C and the larvae were fed the correct powdered feed daily. Hormonal activity is expressed as the percentage decrease, relative to the control, in the number of morphologically normal adults emerging from the cocoon, determined after the leak of the insects not treated with the product j 25 (control) from the cocoon had ended completely (about 14 days after the start of the test).

Compounds No. 1, 2, 3, 4, 6, 8, 10, 11, 14, 16, 19, 20 21, 33, 37, 38 and 39 showed complete activity (100%) at a dose of 2 ppm.

5 ml of an acetone product solution were introduced into pots each containing 250 g of larval brood feed, whereupon has been thoroughly mixed. The control was used in the same way, but the treatment was only carried out with Acetone.

The feed in each pot was infected with 100 2-day-old larvae and kept at 25 + 1 ⁰ C and 65 + 5% relative humidity. After 60 days, the pupae present in the food were collected and transferred to another pot, whereupon one waited for the cocoon to emerge.

The hormone activity is expressed as the percentage reduction relative to the control, the number of morphologically nor ₁₀ painter adult, which emerge from the cocoon, determined after from leakage of the non-treated with the product insects (control) was complete from the cocoon (about 10 days after the start of the test).

! ₁₅ Compounds No. 1, 2, 3 and 30 showed complete activity (100%) at a dose of 20 ppm.

5 ml of an acetonic product solution were added to pots each containing 5 g of wheat flour, and the mixture was then carefully mixed. The control was carried out in the same way, but the treatment was only carried out with acetone. After evaporation of the solvent, the wheat flour was carefully mixed again and infected with 25 larvae of 20-22 days of age. The samples were kept at 25 + l relative ° C and 65 + 5% ²⁵ humidity.

The hormonal activity is expressed as the percentage reduction, relative to the control, of the number morphologically

j normal adult escaping from the cocoon, determined as escaping insects not treated with the product (Control) was completely finished (about 45 days after test determined.

Compounds No. 1, 2, 3, 4, 5, 6, I ₁ 11, 12, 21, 22, 27, ³⁵ 29, 31, 32, 33, 34, 35, 36 and 37 showed complete activity (100 %) at a dose of 200 ppm, most of which were still fully effective at only 20 ppm.

Determination of acaricidal activity

Small bean leaf disks 2.5 cm in diameter were infected with approximately 20 adult females per disk. After 24 hours, the mites were removed and the discs containing the eggs were treated by immersion in an aqueous / acetone product solution (10% acetone). The control was carried out in the same way, but the treatment was only carried out with an aqueous / acetone solution. The treated disks were kept at 23 + 1 ⁰ C and 70 + 5% relative humidity.

The activity is expressed as the percentage reduction, based on the control, of the number of eggs hatched, determined when the hatching of the eggs not treated with the product (control) was completely finished (about 7 days after the start of the test).

Connections No. 1, 2, 3, 4, 14, 15, 17, 19, 20, 23, 24, 25, 26, 31, 33, 36 and 38 showed complete activity (100%) at a dose of 0.1%.

In the above formulas, alkyl radicals with 1-5 carbon atoms mean e.g. methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl, pentyl, i-pentyl; Alkyl in the more complex radicals, such as alkylthio, haloalkyl or alkylcarbonyl, has the same meaning.

Halogen is in particular Cl, F, Br.
3oThe haloalkyl group can contain 1, 2 or 3 halogen atoms.

Alkenyl is, for example, ethylene, propylene -1 or -2, butylene-2 or -1 and pentylene.

Alkynyl radicals are, for example, ethynyl, propynyl, butynyl or Pertinyl.

Claims (14)

Paten t claims
1.J- A compound of the formula Ol IO1 f (D O-C-C ^ C-R in which R = a 2-furyl, 2-thienyl, pyridyl or phenyl radical, where the pyridyl or phenyl radical is optionally replaced by one or more groups selected from C _1-5 alkyl, C _1-5 haloalkyl with 1 to 3 halogen atoms, C " _c alkenyl, C _{0 c} haloalkenyl with 1 to 3 halogen atoms, C _3-5 alkynyl, C ^ _ ₅ alkoxy, C, _c haloalkoxy with 1 to 3 halogen atoms, C _1-5 alkyl thio, alkoxycarbonyl with 1 to 5 carbon atoms in the alkoxy part, Alkylcarbonyl with 1 to 5 carbon atoms in the alkyl part, nitro, cyano and halogen, can be substituted X = an oxygen atom or a divalent sulfur atom; 1 2
R and R = which are the same or different from one another, a hydrogen atom or a methyl or ethyl group. mean. 2. A compound according to Claim 1 in which X is an oxygen atom.
3. A compound according to claim 1 in which X is a is divalent sulfur atom. 4.- A compound according to claim 1, in which R = R = H is. 5, - A compound according to claim 1, in which R = CH_ 2 ^y and R = H. 1 6.- A compound according to claim 1, in which R = R = CH. 12 7, - A compound according to claim 2, in which R = R = H is. 8.- 1-Phenoxy-4- / I- (2-pyridyl) -prop-2-ynyl-oxy7-benzene. 9.- 1-Phenoxy-4- / 3- (4-methoxyphenyl) -prop-2-ynyl-oxy7-benzene. 10. - 1-Phenoxy-4- / 3- (4-methylphenyl) -prop-2-ynyl-oxy_7-benzene. 11.- 1-Phenoxy-4- ^ 1- (4-nitropheny1) -prop-2-yny1-oxy / benzene. 12.-1-Phenoxy-4 - / (3-phenyl-prop-2-ynyl-oxy) 7-benzene. 13.- A method for combating insect or acarid infestation, characterized in that one is on the infected Provides an effective amount of one or more compounds according to claim 1 per se or as a suitable composition distributed. 14.- Insecticidal or acaricidal composition containing one or more compounds according to claim 1 as active Component together with a liquid or solid inert carrier, also from a food or feed origin, and optionally other additives commonly used in these formulations.